DALLAS, July 26, 2021 – People who are just starting treatment for high blood pressure can benefit equally from two different classes of drugs – angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) – but are ARBs may be less likely to cause drug side effects, according to an analysis of real-world data published today in Hypertension, a journal of the American Heart Association.
While the class of antihypertensive drugs called angiotensin converting enzyme (ACE) inhibitors may be prescribed more often, angiotensin receptor blockers (ARBs) work just as well and may cause fewer side effects. Currently, ACE inhibitors are prescribed more often than ARBs as the first drug for controlling blood pressure.
The results are based on an analysis of eight electronic health records and insurance claims databases in the US, Germany and South Korea, which include nearly 3 million patients taking a high blood pressure drug for the first time with no history of heart disease or stroke.
Both types of drugs work on the renin-angiotensin-aldosterone system, a group of related hormones that work together to regulate blood pressure. ACE inhibitors lower blood pressure by blocking an enzyme early in the system so that less angiotensin, a chemical that narrows blood vessels, is made and blood vessels can stay wider and more relaxed. ARBs block receptors in the blood vessels that angiotensin binds to, reducing its vasoconstricting effects.
“The professional guidelines recommend multiple classes of drugs equally as first-line therapies. With so many drugs to choose from, we felt we could provide clarity and guidance to patients and healthcare professionals,” said RuiJun Chen, MD, MA, lead study author, assistant professor in Translational Data Science and Computer Science at Geisinger Medical Center in Danville, Pennsylvania, and NLM Postdoctoral Fellow at Columbia University at the time of the study.
The AHA / ACC 2017 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults says that the primary drugs used to treat high blood pressure are thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers as they have been shown to reduce cardiovascular events. Physical activity and other lifestyle changes are recommended to manage all levels of high blood pressure, even when medication is required.
For this study, medical records were reviewed for patients who began initial antihypertensive treatment with a single drug between 1996 and 2018. The researchers compared the incidence of heart-related events and stroke in 2,297,881 patients treated with ACE inhibitors with those of 673,938 patients treated with ARBs. Heart-related events include heart attack, heart failure, or stroke, or a combination of these events, or sudden cardiac death that is recorded in the database. The researchers also compared the incidence of 51 different side effects between the two groups. The follow-up times varied in the database entries, but ranged from about 4 months to more than 18 months.
They found no significant differences in the occurrence of myocardial infarction, stroke, hospitalization for heart failure or other cardiac events. However, they found significant differences in the incidence of four drug side effects. Compared to those who took ARBs, the people who took ACE inhibitors were:
- 3.3 times more frequent accumulation of fluid and swelling of the deeper skin and mucous membrane layers (angioedema);
32% more likely to develop a cough (which can be dry, persistent, and bothersome);
32% more likely to develop sudden inflammation of the pancreas (pancreatitis); and
18% increased incidence of gastrointestinal bleeding;
“We didn’t see a difference in the way the two types of medication reduce the complications of high blood pressure, but we did see a difference in the side effects,” said George Hripcsak, MD, lead author of the study and professor and chair of Biomedical Informatics at Columbia University Vagelos College of Physicians and Surgeons and Director of Medical Informatics at Irving Medical Center, New York-Presbyterian / Columbia University. “When a patient first starts hypertension therapy, our results suggest that the ARB is started over the ACE inhibitor.”
“ARBs are no different in effectiveness and may have fewer side effects than ACE inhibitors in those just starting treatment,” said Chen. “Unfortunately, we cannot apply these conclusions to people who are already taking ACE inhibitors or multiple drugs. Once again, we would like to remind you that if you notice any side effects of your medicine you should discuss with your doctor whether your antihypertensive therapy may be required. “
The study was limited by large differences in the length of time patients were enrolled in the various databases. Although many patients have been followed for long periods of time, those who had shorter follow-up periods may not have taken the medication long enough to experience its full benefits in preventing cardiovascular disease. Most of the participants taking ACE inhibitors (80%) were taking lisinopril, and the most commonly used ARB (45% of those taking this class of drugs) was losartan, so the results may not be fully transferable to other drugs in these classes are. It is also important to note that the results of this first-line therapy analysis may not generalize to people with high blood pressure who have been prescribed combination therapy or who are switching from one type of drug to another.
“In addition to encouraging patients to lead healthy lifestyles and take medication to control blood pressure, the American Heart Association recommends regular blood pressure monitoring with a validated device and working with a healthcare professional on a plan to lower blood pressure,” said Willie Lawrence, MD, interventional cardiologist and medical director for Health Equity, Spectrum Health, Benton Harbor, Michigan, and chairman of the supervisory committee of the American Heart Association’s National Hypertension Control Initiative.
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Co-authors are Marc A. Suchard, MD, Ph.D .; Harlan M. Krumholz, MD, SM; Martijn J. Schuemie, Ph.D .; Steven Shea, MD; Jon Duke, MD; Nicole Pratt, Ph.D .; Christian G. Reich, MD, Ph.D .; David Madigan, Ph.D .; Seng Chan You, MD; and Patrick B. Ryan, Ph.D. Details are in the manuscript.
The study was supported by the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health, Social Affairs and Commerce, Industry and Energy of the Republic of Korea.
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DOI
10.1161 / HYPERTENSIONAHA.120.16667.
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